The research proposed has two complementary goals. The first goal is to[unreadable] elucidate the biological properties of adult stem cells (ASCs) that renew human tissues. The[unreadable] second is to translate human ASC discoveries into advances in cellular medicine. For decades,[unreadable] lack of critical knowledge about ASCs has been a formidable wall at the frontier of ASC[unreadable] research and cellular medicine. Three intractable research challenges form this wall. Methods[unreadable] for exact identification of ASCs are lacking, ASCs are difficult to produce in large quantities,[unreadable] and, therefore, important biological features of ASCs remain obscure. To address these[unreadable] challenges, during the past 14 years as a principal investigator, the applicant undertook[unreadable] research with genetically-engineered mouse cells that modeled essential unique properties of[unreadable] ASCs. These properties are asymmetric self-renewal and immortal DNA strand co-segregation,[unreadable] two defining features of ASCs. A series of reports from the applicant?s laboratory established[unreadable] the relevance of discoveries made with the mouse ASC models to rodent ASCs in vivo. These[unreadable] discoveries established an innovative foundation for identifying ASCs, expanding ASCs in[unreadable] culture, and investigating ASC cellular and molecular properties. With NDPA support, the[unreadable] applicant will change the direction of his research program, forged with rodent ASC studies, to[unreadable] focus on human ASCs and their conversion into embryonic stem cell (ESC)-like cells. Human[unreadable] ASCs responsible for liver, hematopoietic cells, pancreas, and hair will be the focus of research[unreadable] with the goal of developing both pre-clinical and clinical applications for cellular medicine. The[unreadable] applicant?s research program enjoys collaborations with several laboratories from diverse[unreadable] scientific disciplines and technological fields, including mathematics, chromosome biology,[unreadable] mass spectrometry, bioinformatics, genomics, electrical engineering, computer sciences, and[unreadable] the cell products industry. These interactions will complement research to expand selected[unreadable] human ASCs, develop tools for their exact identification, and advance ASCs as effective cellular[unreadable] medicines for human disease.